Cdk2 Phosphorylation on Threonine39 by AKT and Its Implication on Cyclin Binding, Cellular Localization, and Cell Cycle Progression
Abstract
One of the hallmarks of cancer is the deregulation of the cell proliferation. This deregulation promotes genetic errors that contribute to genomic instability. Our hypothesis is that Cdk2 exists in two freely exchangeable conformations: that seen in the active, cyclin-bound crystal and that of the inactive monomeric Cdk2, with the latter predominating in the absence of cyclin. We propose that phosphorylation of Cdk2T39 shifts the equilibrium in the direction of the active conformation that best fits cyclin and therefore facilitating cyclin binding, G1 progression and initiation of DNA synthesis. We will test this hypothesis by treating recombinant cdk2 with AKT and sending it for mass spectroscopy so we can determine if Cdk2 is indeed phosphorylated by AKT. We will also determine the effect of AKT phosphorylation on Cdk2 by constructing a phosphomimetic mutant of Cdk2 and determining if this has an effect on cyclin binding and G1 progression. Ultimately, this research may elucidate a novel method of cell cycle control through which mitogenic signals may influence the cell cycle.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2008
- Accession Number
- ADA545076
Entities
People
- Thiago Dasilva
Organizations
- University of Miami